Azole derivative and azole mycocide

ABSTRACT

Disclosed herein are azole derivatives or the salts thereof which are represented by the general formula (I): ##STR1## wherein X represents a halogen atom, an alkyl group having 1 to 5 carbon atoms, a haloalkyl group, a phenyl group, a cyano group, or a nitro group, Xs being either the same or different from each other; n represents an integer of 1 to 5; A represents a nitrogen atom or CH; and one of R 1  and R 2  represents an alkyl group having 1 to 5 carbon atoms and the other a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, with the proviso that when n is 1 or 2, X does not represent a halogen atom, an alkyl group having 1 to 5 carbon atoms or a phenyl group, and mycocides comprising an effective amount of azole derivative or medically or veterinarily acceptable salt thereof, said azole derivative being represented by the general formula (II): ##STR2## wherein X represents a halogen atom, an alkyl group having 1 to 5 carbon atoms, a haloalkyl group, a phenyl group, a cyano group, or a nitro group, Xs being either the same or different from each other; n represents an integer of 0 to 5; A represents a nitrogen atom or CH; and R 1  and R 2  respectively represent a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, and a diluent or a carrier which is medically or veterinarily acceptable.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a division of earlier application Ser. No.07/666,488 filed Mar. 6, 1991, now U.S. Pat. No. 5,162,356 which, inturn, is a continuation of application Ser. No. 07/201,982 filed Jun. 3,1988, now abandoned.

BACKGROUND OF THE INVENTION

The present invention relates to azole derivatives or the salts thereofwhich are represented by the formula (I): ##STR3## wherein X representsa halogen atom, an alkyl group having 1 to 5 carbon atoms, a haloalkylgroup, a phenyl group, a cyano group, or a nitro group, Xs being eitherthe same or different from each other; n represents an integer of 1 to Arepresents a nitrogen atom or CH; and one of R₁ and R₂ represents analkyl group having 1 to 5 carbon atoms and the other a hydrogen atom oran alkyl group having 1 to 5 carbon atoms, with the proviso that when nis 1 or 2, X does not represent a halogen atom, an alkyl group having 1to 5 carbon atoms or a phenyl group and mycocides useful for animalsincluding man, which contain as an effective ingredient an effectiveamount of azole derivative represented by the formula (II): ##STR4##wherein X represents a halogen atom, an alkyl group having 1 to 5 carbonatoms, a haloalkyl group, a phenyl group, a cyano group, or a nitrogroup, Xs being either the same or different from each other; nrepresents an integer of 0 to 5; A represents a nitrogen atom or CH; andR₁ and R₂ respectively represent a hydrogen atom or an alkyl grouphaving 1 to 5 carbon atoms or a salt thereof which is medically orveterinarily acceptable.

The fact that a part of the compounds represented by the formula (II)have action of protecting plants from phytopathogens, growth-regulatingeffects and herbicidal effects on plants as agricultural andhorticultural chemicals has already been reported together with themethods for producing the compounds by the present inventors (JapanesePatent Application Nos. 60-202431 (1985) and 61-265559 (1986)).

As a result of further studies of the adaptability of the compoundsdisclosed in Japanese Patent Application Nos. 60-202431 (1985) and61-265559 (1986) and novel compounds to fields other than the fields ofagricultural and horticultural chemicals, the present inventors havefound that the known compounds and novel compounds represented by theformula (I) have mycocidal effects on animals including man. The presentinvention has been achieved on the basis of this finding.

SUMMARY OF THE INVENTION

In a first aspect of the present invention, there is provided an azolederivative represented by the formula (I): ##STR5## wherein X representsa halogen atom, an alkyl group having 1 to 5 carbon atoms, a haloalkylgroup, a phenyl group, a cyano group, or a nitro group, Xs being eitherthe same or different from each other; n represents an integer of 1 to5; A represents a nitrogen atom or CH; and one of R₁ and R₂

atoms and the represents an alkyl group having 1 to 5 carbon other ahydrogen atom or an alkyl group having 1 to 5 carbon atoms, with theproviso that when n is 1 or 2, X does not represent a halogen atom, analkyl group having 1 to 5 carbon atoms or a phenyl group, and a saltthereof.

In a second aspect of the present invention, there is provided amycocide which comprises an effective amount of azole derivativerepresented by the formula (II): ##STR6## wherein X represents a halogenatom, an alkyl group having 1 to 5 carbon atoms, a haloalkyl group, aphenyl group, a cyano group, or a nitro group, Xs being either the sameor different from each other; n represents an integer of 0 to 5; Arepresents a nitrogen atom or CH; and R₁ and R₂ respectively represent ahydrogen atom or an alkyl group having 1 to 5 carbon atoms, or amedically or veterinarily acceptable salt thereof, and a diluent or acarrier which is medically or veterinarily acceptable.

In a third aspect of the present invention, there is provided a methodfor treating mycosis of man or an animal comprising administering aneffective amount of azole derivative represented by the formula (II):##STR7## wherein X represents a halogen atom, an alkyl group having 1 to5 carbon atoms, a haloalkyl group, a phenyl group, a cyano group, or anitro group, Xs being either the same or different from each other; nrepresents an integer of 0 to 5; A represents a nitrogen atom or CH; andR₁ and R₂ respectively represent a hydrogen atom or an alkyl grouphaving 1 to 5 carbon atoms, or a medically or veterinarily acceptablesalt thereof.

In a fourth aspect of the present invention, there is provided a use ofan azole derivative represented by the formula (II): ##STR8## wherein Xrepresents a halogen atom, an alkyl group having 1 to 5 carbon atoms, ahaloalkyl group, a phenyl group, a cyano group, or a nitro group, Xsbeing either the same or different from each other; n represents aninteger of 0 to 5; A represents a nitrogen atom or CH; and R₁ and R₂respectively represent a hydrogen atom or an alkyl group having 1 to 5carbon atoms, or a medically or veterinarily acceptable salt thereof forproducing a mycocide.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1 to 110 show the infrared absorption spectra of the azolederivative shown in Table 1, wherein FIG. 1 shows the infraredabsorption spectrum of Compound No. 1, FIG. 2 that of Compound No. 2,FIG. 3 that of Compound No. 3, and FIGS. 4 to 110 those of Compound Nos.4 to 110, respectively.

DETAILED DESCRIPTION OF THE INVENTION

The compounds of the present invention and the compounds used in thepresent invention are represented by the following formula (II):##STR9## wherein X represents a halogen atom, an alkyl group having 1 to5 carbon atoms, a haloalkyl group, a phenyl group, a cyano group, or anitro group, Xs being either the same or different from each other; nrepresents an integer of 0 to 5; A represents a nitrogen atom or CH; andR₁ and R₂ respectively represent a hydrogen atom or an alkyl grouphaving 1 to 5 carbon atoms.

Among these, X is preferably a halogen atom or a phenyl group, n ispreferably 1 or 2, and R₁ and R₂ are preferably alkyl groups having 1 to3 carbon atoms.

Since the compounds used in the present invention have an azolylmethylgroup at the 1-position, a hydrogen atom or an alkyl group having 1 to 5carbon atoms at the 2-position, and a substituted benzyl group at the5-position, respectively, of a cyclopentane ring, the compounds havegeometric isomers and optical isomers. The compounds of the presentinvention include all these respective isomers and mixtures of anynumber of isomers in any ratio. Accordingly, the mycocide according tothe present invention may contain a single isomer or a mixture of theseisomers as an effective ingredient.

The compounds of the present invention represented by the formula (I)can be synthesized in accordance with a method described in JapanesePatent Application Nos. 60-202431 (1985) and 61-265559 (1986).

The compounds represented by the formula (II) and the physicochemicalproperties (melting points) thereof are shown in Table 1. "A type" and"B type" in Table 1 represent the following two types. ##STR10##

                                      TABLE 1                                     __________________________________________________________________________    Azole derivative                                                              Compound No.                                                                             R.sub.1                                                                             R.sub.2                                                                              X.sub.n                                                                             A   Type of stereo-isomer                                                                    Melting point                    __________________________________________________________________________                                                 (°C.)                     1          CH.sub.3                                                                            CH.sub.3                                                                             4-Cl   N  A          113-114                          2          CH.sub.3                                                                            CH.sub.3                                                                             4-Cl  N   B          113-114                          3          CH.sub.3                                                                            CH.sub.3                                                                             4-Cl  CH  A          133-134                          4          CH.sub.3                                                                            CH.sub.3                                                                             4-Cl  CH  B          133-134                          5          CH.sub.3                                                                            CH.sub.3                                                                             4-Br  N   A          129-130                          6          CH.sub.3                                                                            CH.sub.3                                                                             4-Br  N   B          134-135                          7          CH.sub.3                                                                            CH.sub.3                                                                             4-Br  CH  A          149-150                          8          CH.sub.3                                                                            CH.sub.3                                                                             4-Br  CH  B          134-135                          9          CH.sub.3                                                                            CH.sub.3                                                                             4-F   N   A          135-136                          10         CH.sub.3                                                                            CH.sub.3                                                                             4-F   N   B          134-135                          11         CH.sub.3                                                                            CH.sub.3                                                                             4-F   CH  A          131-133                          12         CH.sub.3                                                                            CH.sub.3                                                                             4-F   CH  B          104-106                          13         CH.sub.3                                                                            CH.sub.3                                                                             2,4-Cl.sub.2                                                                        N   A          126-127                          14         CH.sub.3                                                                            CH.sub.3                                                                             2,4-Cl.sub.2                                                                        N   B          108-110                          15         CH.sub.3                                                                            CH.sub.3                                                                             2,4-Cl.sub.2                                                                        CH  A          131-132                          16         CH.sub.3                                                                            H      4-Cl  N   A          100-102                          17         CH.sub.3                                                                            H      4-Cl  CH  A          118-119                          18         H     CH.sub.3                                                                             4-Cl  N   A          75-76                            19         H     CH.sub.3                                                                             4-Cl  N   B          79-81                            20         CH.sub.3                                                                            H      4-Cl  N   B          Oily matter                      21         CH.sub.3                                                                            CH.sub.3                                                                             H     N   A          Oily matter                      22         CH.sub.3                                                                            CH.sub.3                                                                             H     CH  A          128-130                          23         CH.sub.3                                                                            CH.sub.3                                                                             4-CH.sub.3                                                                          N   A          123-124                          24         CH.sub.3                                                                            CH.sub.3                                                                             4-CH.sub.3                                                                          N   B          114-115                          25         CH.sub.3                                                                            CH.sub.3                                                                             4-CH.sub.3                                                                          CH  A          132-133                          26         CH.sub.3                                                                            CH.sub.3                                                                             4-CH.sub.3                                                                          CH  B          130-131                          27         CH.sub.3                                                                            CH.sub.3                                                                             2-F, 4-Cl                                                                           N   A          129-130                          28         CH.sub.3                                                                            CH.sub.3                                                                             2-F, 4-Cl                                                                           CH  A          152-154                          29         C.sub.2 H.sub.5                                                                     H      4-Cl  N   A          82-84                            30         H     C.sub.2 H.sub.5                                                                      4-Cl  N   A          93-95                            31         H     C.sub.2 H.sub.5                                                                      4-Cl  N   B          76-78                            32         C.sub.2 H.sub.5                                                                     H      4-Cl  N   B          110-112                          33         C.sub.2 H.sub.5                                                                     C.sub.2 H.sub.5                                                                      4-Cl  N   A          124-126                          34         C.sub.2 H.sub.5                                                                     C.sub.2 H.sub.5                                                                      4-Cl  N   B          143-145                          35         C.sub.2 H.sub.5                                                                     C.sub.2 H.sub.5                                                                      4-Cl  CH  A          Oily matter                      36         C.sub.2 H.sub.5                                                                     C.sub.2 H.sub.5                                                                      4-Cl  CH  B          143-145                          37         n-C.sub.3 H.sub.7                                                                   H      4-Cl  N   A          83-85                            38         H     n-C.sub.3 H.sub.7                                                                    4-Cl  N   A          75-77                            39         n-C.sub.3 H.sub.7                                                                   H      4-Cl  CH  A          115-117                          40         C.sub.2 H.sub.5                                                                     H      2,4-Cl.sub.2                                                                        N   A          124-127                          41         C.sub.2 H.sub.5                                                                     H      2,4-Cl.sub.2                                                                        CH  A          111-113                          42         C.sub.2 H.sub.5                                                                     H      4-F   N   A          73-74                            43         C.sub.2 H.sub.5                                                                     H      4-F   CH  A          111-113                          44         C.sub.2 H.sub.5                                                                     H      4-Br  N   A          80-82                            45         C.sub.2 H.sub.5                                                                     H      4-Br  CH  A          117-119                          46         C.sub.2 H.sub.5                                                                     H      4-C.sub.6 H.sub.5                                                                   N   A          107-109                          47         C.sub.2 H.sub.5                                                                     H      4-C.sub.6 H.sub.5                                                                   CH  A          169-170                          48         C.sub.2 H.sub.5                                                                     H      4-t-C.sub.4 H.sub.9                                                                 N   A          Oily matter                      49         C.sub.2 H.sub.5                                                                     H      4-t-C.sub.4 H.sub.9                                                                 CH  A          132-133                          50         i-C.sub.3 H.sub.7                                                                   H      4-Cl  N   A          91-92                            51         n-C.sub.5 H.sub.11                                                                  H      4-Cl  N   A          Oily matter                      52         n-C.sub.5 H.sub.11                                                                  H      4-Cl  CH  A          92-95                            53         C.sub.2 H.sub.5                                                                     H      4-Cl  CH  B          138-140                          54         H     n-C.sub.5 H.sub.11                                                                   4-Cl  N   A          Oily matter                      55         CH.sub.3                                                                            CH.sub.3                                                                             4-C.sub.6 H.sub. 5                                                                  N   A          122-124                          56         CH.sub.3                                                                            CH.sub.3                                                                             4-C.sub.6 H.sub.5                                                                   N   B          116-118                          57         CH.sub.3                                                                            CH.sub.3                                                                             4-C.sub.6 H.sub.5                                                                   CH  A          162-163                          58         CH.sub.3                                                                            CH.sub.3                                                                             4-C.sub.6 H.sub.5                                                                   CH  B          165-167                          59         i-C.sub.3 H.sub.7                                                                   H      4-Cl  CH  A          Oily matter                      60         CH.sub.3                                                                            CH.sub.3                                                                             4-t-C.sub.4 H.sub.9                                                                 N   A          107-108                          61         CH.sub.3                                                                            CH.sub.3                                                                             4-t-C.sub.4 H.sub.9                                                                 CH  A          167-168                          62         H     i-C.sub.3 H.sub.7                                                                    4-Cl  N   B          Oily matter                      63         H     i-C.sub.3 H.sub.7                                                                    4-Cl  N   A          102-103                          64         H     i-C.sub.3 H.sub.7                                                                    4-Cl  CH  A          146-147                          65         i-C.sub.3 H.sub.7                                                                   H      4-Cl  N   B          120-121                          66         n-C.sub.4 H.sub.9                                                                   H      4-Cl  CH  A          Oily matter                      67         H     n-C.sub.4 H.sub.9                                                                    4-Cl  N   A          94-95                            68         H     n-C.sub.4 H.sub.9                                                                    4-Cl  N   B          Oily matter                      69         i-C.sub.4 H.sub.9                                                                   H      4-Cl  N   A          Oily matter                      70         i-C.sub.4 H.sub.9                                                                   H      4-Cl  CH  A          Oily matter                      71         n-C.sub.4 H.sub.9                                                                   H      4-Cl  N   A          Oily matter                      72                                                                            Isomer a   CH.sub.3                                                                            C.sub.2 H.sub.5                                                                      4-Cl  N   A          72-a, 72-b                                                                    mixture                          Isomer b   C.sub.2 H.sub.5                                                                     CH.sub.3                                                                             4-Cl  N   A           98-101                          73                                                                            Isomer a   CH.sub.3                                                                            C.sub.2 H.sub.5                                                                      4-Cl  N   B          73-a, 73-b,                                                                   Mixture                          Isomer b   C.sub.2 H.sub.5                                                                     CH.sub.3                                                                             4-Cl  N   B          117-119                          74                                                                            Isomer a   CH.sub.3                                                                            C.sub.2 H.sub.5                                                                      4-Cl  N   B          74-a, 74-b,                                                                   Mixture                          Isomer b   C.sub.2 H.sub.5                                                                     CH.sub.3                                                                             4-Cl  N   B          122-127                          75         CH.sub.3                                                                            CH.sub.3                                                                             4-t-C.sub.4 H.sub.9                                                                 N   B          Oily matter                      76         CH.sub.3                                                                            CH.sub.3                                                                             4-t-C.sub.4 H.sub.9                                                                 CH  B          132-133                          77         H     H      H     N   A          140-141                          78         H     H      H     CH  A          130-131                          79         H     H      4-CH.sub.3                                                                          N   A          128-129                          80         H     H      4-CH.sub.3                                                                          CH  A          122-123                          81         H     H      4-t-C.sub.4 H.sub.9                                                                 N   A          129-130                          82         H     H      4-t-C.sub.4 H.sub.9                                                                 CH  A          123-124                          83         H     H      2-Cl  N   A          154-155                          84         H     H      2-Cl  CH  A          103-104                          85         H     H      3-Cl  N   A          152-153                          86         H     H      3-Cl  CH  A          105-106                          87         H     H      4-Cl  N   A          115-116                          88         H     H      4-Cl  CH  A          115-116                          89         H     H      2,4-Cl.sub.2                                                                        N   A          120-121                          90         H     H      2,4-Cl.sub.2                                                                        CH  A          150-151                          91         H     H      4-F   N   A          135-136                          92         H     H      4-F   CH  A          139-140                          93         H     H      2,4-F.sub.2                                                                         N   A          118-119                          94         H     H      2,4-F.sub.2                                                                         CH  A          144-145                          95         H     H      2,6-F.sub.2                                                                         N   A          104-105                          96         H     H      2,6-F.sub.2                                                                         CH  A          150-151                          97         H     H      3,4-F.sub.2                                                                         N   A          119-121                          98         H     H      3,4-F.sub.4                                                                         CH  A          103-105                          99         H     H      2,3,4,                                                                              N   A          118-120                                                  5,6-F.sub.5                                           100        H     H      3-CF.sub.3                                                                          N   A          152-153                          101        H     H      3-CF.sub.3                                                                          CH  A          87-88                            102        H     H      2-F, 4-Cl                                                                           N   A          125-127                          103        H     H      2-F, 4-Cl                                                                           CH  A          141-143                          104        H     H      4-Br  N   A          106-107                          105        H     H      4-Br  CH  A          119-120                          106        H     H      4-C.sub.6 H.sub.5                                                                   N   A          146-147                          107        H     H      4-C.sub. 6 H.sub.5                                                                  CH  A          182-183                          108        H     H      4-NO.sub.2                                                                          N   A          131-132                          109        H     H      4-CN  N   A          115-116                          110        H     H      4-CN  CH  A          103-104                          __________________________________________________________________________

Medicines which contain a compound represented by the general formula(II) or medically or veterinarily acceptable salt thereof, e.g.,a saltof an inorganic acid such as a nitric acid, sulfuric acid andhydrochloric acid and a salt of an organic acid such as a fumaric acidand naphthalene-1,5-disulfonic acid and a diluent or a carrier which ismedically or veterinarily acceptable are medicines which show amycocidal activity and are useful for treating mycosis of animalsincluding man. For example, these medicines are useful for treating alocal mycosis of man caused by a fungus belonging to the genus such asCandida, Trichophyton, Microsporum and Epidermophyton or a mucosalmycosis caused by C. albicans, e.g., candidiasis of mouth andcandidiasis of vagina. These medicines can also be used for treating asystemic mycosis caused by C. albicans, Cryptococcus neoformans,Aspergillus fumigatus, or a fungus belonging to genus such asCoccidioides, Paracoccidiodes, Histoplasma and Blastomyces.

When the compounds represented by the formula (II) is used for man, theymay be used singly, but they are generally administered in the form of amixture with a carrier and/or diluent which is selected in accordancewith desired administration route and unit dosage form. For example,these compounds may be orally administered in the form of a tabletcontaining an excipient such as starch and lactose, in the form of acapsule or ovules in a single state or in a state of being mixed with anexcipient, or in the form of an elixir or a suspension containing aflavor or coloring agent. These compounds may also be parenterallyadministered, for example, by intravenous injection, subcutaneousinjection, intramascular injection or the like. In the case ofadministering such a medicine parenterally, it is most preferable thatthe medicine is used in the form of a germfree aqueous solutioncontaining a sufficient amount of salt or glucose for making aninjection solution isotonic with blood.

The compounds represented by the formula (II) may also be administeredin the form of a suppository or a vaginal suppository, or applied to theaffected part in the form of a lotion, liquid, cream, ointment ordusting powder. For example, these compounds may be added to a creamcomprising an aqueous emulsion of polyethylene glycol or liquidparaffin. These compounds may also be added in the range of 1 to 10%concentration to an ointment comprising white Japan wax or white liquidparaffin and necessary stabilizer and antiseptic.

The ordinary dosage of the compound represented by the formula (II) forman is 0.1 to 40 mg/kg per day, whether it is administered orally orparenterally. It is therefore possible to use a tablet or a capsule ofthis compound which contains 1 mg to 0.5 g of the compound in order toadminister one or more of them every time, as occasion demands. Theactual optimum dosage is judged by a doctor in accordance with the age,weight, sensitivity, and degree of infection of the patient. Theabove-described dosage is for an average case, and the effective rangeof dosage naturally fluctuates depending on cases, such range beingincluded in the present invention.

These compounds may be administered to animals other than man by thesame administration methods and dosage (0.1 to 40 mg/kg.day) as in thecase of man.

The mycocidal activity in vitro of the compounds represented by theformula (II) can be evaluated by measuring the minimum inhibitoryconcentration (hereinunder referred to as "M.I.C.") of the testcompounds for inhibiting the growth of a specific fungus in anappropriate culture medium. Actually, standard culture of C. albicans,for example, is inoculated into a series of agar plates containing testcompounds in a predetermined concentration. After each agar plate iscultivated at a predetermined temperature for a predetermined time,whether C. albicans has grown or not is examined to determine the M.I.C.of the corresponding compound. Other fungi such as Cryptococcusneoformans, Candida spp.,Torulopsis glabrata, Aspergillusspp.,Cladosporium carrionii, Fonsecaea pendrosoi, Microsporum spp., E.floccosum, Phialophora verrucosa, C. immitis and Sporothrix schenckiiare also usable in this kind of test.

The effectiveness of the compounds represented by the formula (II) tofungi will now be shown with reference to the following non-limitativeexamples.

EXAMPLE 1

The anti-fungus activities in vitro of the compounds represented by theformula (II) were examined. Testing method:

Each of the compounds shown in Table 2 was dissolved indimethylsulfoxide so as to have a predetermined concentration. In apetri dish, were well mixed 0.1 m(of the compound and 9.9 ml Sabouraud'sagar culture medium of about 60° C. to be solidified. The spores of atest fungus which had been cultivated in a plate culture medium at 28°C. for 20 to 30 days was suspended in 0.1% Tween 80 solution(Polyoxyeth-ylene Sorbitan Monooleate). The suspension was adjusted byusing 0.1% Tween 80 solution so as to have a spore concentration of 10⁵to 10⁶ spores/ml. Into the plate medium containing the test compound, 5μl of the fungus suspension was inoculated. After the inoculation, thefungus was cultivated at 28° C. Whether the fungus had grown or not wasjudged 4 days after the inoculation in the case of Aspergillus, and 7days after the inoculation in the case of the other fungi to obtain theM.I.C.

The degree of growth inhibition was evaluated into 5 stages inaccordance with the following standards. The results are shown in Table2.

Growth inhibition

5 M.I.C<3.13 ppm

4 3.13 ppm≦M.I.C.<12.5 ppm

3 12.5 ppm≦M.I.C.<50 ppm

2 50 ppm≦M.I.C.<=100 ppm

1 100 ppm<M.I.C.

                  TABLE 2                                                         ______________________________________                                               Test fungus                                                            Compound A.     A.     C.   F.   M.   P.   T.   T.                            No.      fla.   nig.   car. pen. gyp. ver. men. rub.                          ______________________________________                                         3       5      4      4    5    3    4    4    4                              7       5      5      5    5    5    5    5    5                             11       5      4      5    5    5    4    5    5                             13       4      3      2    3    3    1    3    3                             15       5      4      4    4    5    3    5    5                             16       5      5      5    5    5    5    5    5                             17       5      4      4    5    4    4    5    5                             29       4      3      4    4    4    3    4    4                             35       5      5      5    5    4    5    5    4                             37       5      4      4    4    4    3    4    4                             39       5      5      5    5    5    5    5    5                             41       4      3      3    3    4    3    5    4                             45       5      5      5    5    5    4    5    5                             47       5      5      5    5    5    5    5    5                             52       5      5      5    5    5    5    5    5                             57       5      5      5    5    5    5    5    5                             59       5      5      5    5    5    5    5    5                             71       5      3      5    5    5    3    4    4                             107      5      5      5    5    4    5    5    5                             ______________________________________                                    

Explanation of Abbreviations:

A.fla.; Aspergillus flavus

A.nig.; Aspergillus niger

C.car.; Cladosporium carrionii

F.pen.; Fonsecaea pendrosoi

M.gyp.; Microsporium gypseum

P.ver.; Phialophora verrucosa

T.men.; Trichophyton mentagrophytes

T.rub.; Trichophyton rubrum

EXAMPLE 2

The anti-yeast fungal activities in vitro of the compounds representedby the formula (II) were examined. Testing method:

Each of the compounds shown in Table 3 was dissolved indimethylsulfoxide so as to have a predetermined concentration. In apetri dish, were well mixed 0.1 ml of the compound and 9.9 mlSabouraud's agar culture medium of about 60° C. to be solidified. A testfungus which had been cultivated in a liquid culture medium in advancewas suspended in a physiological saline solution so as to have a fungusconcentration of 105 to 106 cells/ml. Into the plate culture mediumcontaining the test compound shown in Table 3, 5 μl of the fungussolution was inoculated. After the inoculation, the fungus wascultivated at 37° C. for 2 days. Whether the fungus had grown or not wasjudged to obtain the M.I.C.

The degree of growth inhibition was evaluated into 5 stages inaccordance with the following standards. The results are shown in Table3.

Growth inhibition

5 M.I.C.<3.13 ppm

4 3.13 ppm≦M.I.C.<12.5 ppm

3 12.5 ppm≦M.I.C.<50 ppm

2 50 ppm≦M.I.C.≦100 ppm

1 100 ppm<M.I.C.

                  TABLE 3                                                         ______________________________________                                        Com-  Test fungus                                                             pound C.     C.     C.   C.   C.   C.   C.   T.   C.                          No.   alb.   ste.   pse. par. tro. kru. gui. gla. neo.                        ______________________________________                                         1    2      2      3    4    3    4    4    3    5                            3    3      3      4    4    4    5    5    5    5                            4    3      3      3    3    3    3    3    3    4                            5    2      2      3    3    3    4    4    4    5                            6    2      3      3    2    1    1    3    3    3                            7    3      3      4    5    4    5    5    4    5                            8    3      3      3    3    2    3    3    3    4                            9    2      2      2    3    2    3    4    3    4                           10    2      2      2    2    2    2    3    2    3                           11    2      2      3    3    2    4    4    4    4                           12    2      2      2    2    2    2    3    2    3                           13    3      3      3    1    1    1    3    2    3                           14    3      3      3    1    1    1    2    2    3                           15    3      3      4    4    3    4    4    3    4                           16    2      2      2    2    1    3    3    2    4                           17    3      4      3    4    3    4    4    4    4                           19    3      3      2    1    1    1    2    1    4                           21    3      5      2    2    2    3    3    3    5                           22    3      5      3    4    3    4    3    4    5                           23    2      2      2    2    2    2    2    3    3                           25    3      4      4    5    4    5    4    5    5                           26    3      3      3    3    2    3    3    3    4                           27    3      3      3    3    3    4    3    3    4                           28    4      5      4    5    4    5    5    4    5                           29    4      5      3    4    3    4    3    4    5                           30    4      5      3    4    3    5    4    4    5                           31    3      5      3    2    2    2    3    2    5                           32    4      5      3    3    3    3    4    3    5                           33    4      3      3    4    3    4    4    4    4                           34    3      2      2    1    1    2    2    2    4                           36    3      1      4    4    3    4    4    5    4                           37    4      5      3    4    3    5    4    5    5                           38    3      3      3    5    3    5    4    4    5                           39    4      4      4    5    5    5    5    5    5                           40    3      3      3    1    1    1    2    2    4                           41    4      4      4    4    3    4    4    4    5                           42    3      5      2    3    2    3    2    4    5                           43    3      4      3    5    3    5    4    5    4                           44    3      5      3    3    2    4    3    3    5                           45    4      5      3    5    4    5    4    5    5                           47    5      5      5    5    1    4    4    3    5                           48    2      3      2    1    2    1    1    1    5                           49    4      4      4    3    2    2    3    3    5                           50    3      3      2    4    3    4    3    4    4                           51    1      2      1    4    1    3    1    3    2                           52    3      3      4    5    4    5    4    5    5                           53    4      5      4    4    4    4    4    4    5                           54    1      4      1    4    1    4    2    3    5                           57    4      4      4    4    1    4    4    4    5                           58    4      5      4    4    4    4    4    4    5                           59    4      5      4    5    5    5    4    5    5                           60    3      5      3    1    1    1    1    2    5                           61    4      5      5    3    3    3    3    4    5                           63    3      5      3    5    5    5    3    5    5                           64    4      5      4    5    5    5    3    4    5                           65    3      5      3    4    3    3    3    4    5                           66    4      5      5    5    5    5    4    5    5                           67    3      5      3    5    4    4    4    4    5                           68    3      5      3    3    1    1    3    3    5                           69    3      5      3    4    3    4    3    3    5                           70    4      5      5    5    5    5    4    5    5                           71    5      5      3    3    2    5    2    5    5                           75    2      3      3    1    1    1    1    1    4                           76    3      4      4    2    2    2    3    3    5                           80    2      2      2    2    1    2    2    1    3                           82    2      2      3    2    2    2    2    3    3                           84    2      2      3    2    1    1    2    2    2                           86    3      2      3    2    1    1    2    1    3                           87    2      2      2    2    1    2    3    1    3                           90    3      2      3    2    2    2    3    1    2                           92    2      1      2    2    1    2    3    1    2                           97    2      2      2    2    1    1    2    2    1                           98    2      2      2    3    2    2    3    3    1                           101   2      2      3    2    1    1    2    2    2                           102   2      2      2    2    1    2    3    2    2                           103   3      3      3    3    2    3    3    2    2                           104   2      2      2    2    1    2    3    2    3                           105   3      2      3    3    2    3    3    2    3                           107   3      3      4    2    2    3    3    3    4                           ______________________________________                                    

Explanation of abbreviations:

C. alb. : Candida albicans

C. ste. : Candida stellatoidea

C. pse. : Candida pseudotropicalis

C. par. : Candida parapsilosis

C. tro. : Candida tropicalis

C. kru. : Candida krusei

C. gui. : Candida guilliermondii

T. gla. : Torulopsis glabrate

C. neo. : Cryptococcus neoformans

What is claimed is:
 1. A mycocide composition comprising an effectiveamount of an azole derivative represented by the formula: ##STR11##wherein X represents a halogen atom, an alkyl group having 1 to 5 carbonatoms, a halomethyl group, a phenyl group, a cyano group, or a nitrogroup, X being either the same or different from each other; nrepresents an integer of 0 to 5; A represents CH; and one of R₁ and R₂represents an alkyl group having 1 to 5 carbon atoms and the otherrepresents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms,or a medically or veterinarily acceptable salt thereof, and a medicallyor veterinarily acceptable carrier or diluent.
 2. A method for treatingmycosis of man or an animal comprising administering thereto aneffective amount of an azole derivative represented by the formula:##STR12## wherein X represents a halogen atom, an alkyl group having 1to 5 carbon atoms, a halomethyl group, a phenyl group, a cyano group, ora nitro group, X being either the same or different from each other; nrepresents an integer of 0 to 5; A represents CH; and one of R₁ and R₂represents an alkyl group having 1 to 5 carbon atoms and the otherrepresents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms,or a medically veterinarily acceptable salt thereof.